Remodeling of human myocardial collagen in idiopathic dilated cardiomyopathy: Role of metalloproteinases and pyridinoline cross-links

Zeenat Gunja-Smith, Azorides R. Morales, Renzo Romanelli, J. Frederick Woessner

Research output: Contribution to journalArticle

249 Scopus citations

Abstract

A major contribution to the mechanical strength of the heart is provided by a continuous fibrillar collagen network embracing individual myocytes and forming an interstitial and perivascular framework. This study explores the possibility that idiopathic dilated cardiomyopathy may involve extensive changes in this collagenous framework. Idiopathic dilated cardiomyopathy hearts were obtained at transplant and compared with control hearts from autopsy. Idiopathic dilated cardiomyopathy showed a doubling of collagen concentration and a quadrupling of the total collagen per heart, whereas the stable mature cross-link, pyridinoline, diminished from 2.07 mol/mol of collagen to 1.0. Neutrophil-type collagenase activity is elevated approximately 30-fold as is the activity of gelatinase. Tissue inhibitor of metalloproteinase activity falls to negligible levels in idiopathic dilated cardiomyopathy, whereas α2-macroglobulin is high. It is postulated that collagen critical to mechanical stability of the heart is degraded by metalloproteinase activity and is replaced by fibrous intercellular deposits of poorly cross-linked collagen. These changes contribute to weakening and dilatation of the ventricular wall.

Original languageEnglish (US)
Pages (from-to)1639-1648
Number of pages10
JournalAmerican Journal of Pathology
Volume148
Issue number5
StatePublished - May 1 1996

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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